Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia

Journal article


Rolnik, D.L., Wright, D., Poon, L.C., O'Gorman, N., Syngelaki, A., de Paco Matallana, C., Akolekar, R., Cicero, S., Janga, D., Singh, M., Molina, F.S., Persico, N., Jani, J.C., Plasencia, W., Papaioannou, G., Tenenbaum-Gavish, K., Meiri, H., Gizurarson, S., Maclagan, K. and Nicolaides, K.H. 2017. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. The New England Journal of Medicine. 377 (7), pp. 613-622.
AuthorsRolnik, D.L., Wright, D., Poon, L.C., O'Gorman, N., Syngelaki, A., de Paco Matallana, C., Akolekar, R., Cicero, S., Janga, D., Singh, M., Molina, F.S., Persico, N., Jani, J.C., Plasencia, W., Papaioannou, G., Tenenbaum-Gavish, K., Meiri, H., Gizurarson, S., Maclagan, K. and Nicolaides, K.H.
Abstract

BACKGROUND
Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia.

METHODS
In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to
14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle.

RESULTS
A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P = 0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants.
There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events.

CONCLUSIONS
Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo.

KeywordsPreterm preeclampsia; Preeclampsia; Maternal death; Perinatal death; Aspirin; Low-dose aspirin; Double-blind trial; Placebo; Placebo-controlled trial; Singleton pregnancy
Year2017
JournalThe New England Journal of Medicine
Journal citation377 (7), pp. 613-622
PublisherMassachusetts Medical Society
ISSN1533-4406
0028-4793
Digital Object Identifier (DOI)doi:10.1056/NEJMoa1704559
Official URLhttp://doi.org/10.1056/NEJMoa1704559
Publication dates
Print17 Aug 2017
Publication process dates
Deposited15 Jun 2020
Accepted author manuscript
References

1. Duley L. The global impact of preeclampsia and eclampsia. Semin Perinatol
2009;33:130-7.
2. Lisonkova S, Joseph KS. Incidence of
preeclampsia: risk factors and outcomes
associated with early- versus late-onset
disease. Am J Obstet Gynecol 2013;209(6):
544.e1-544.e12.
3. Irgens HU, Reisaeter L, Irgens LM, Lie
RT. Long term mortality of mothers and
fathers after pre-eclampsia: population
based cohort study. BMJ 2001;323:1213-7.
4. Yu CK, Khouri O, Onwudiwe N,
Spiliopoulos Y, Nicolaides KH. Prediction
of pre-eclampsia by uterine artery Doppler imaging: relationship to gestational
age at delivery and small-for-gestational
age. Ultrasound Obstet Gynecol 2008;31:
310-3.
5. Crandon AJ, Isherwood DM. Effect of
aspirin on incidence of pre-eclampsia.
Lancet 1979;1:1356.
6. Askie LM, Duley L, Henderson-Smart
DJ, Stewart LA. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis
of individual patient data. Lancet 2007;
369:1791-8.
7. Meher S, Duley L, Hunter K, Askie L.
Antiplatelet therapy before or after 16
weeks’ gestation for preventing preeclampsia: an individual participant data
meta-analysis. Am J Obstet Gynecol 2017;
216(2):121-128.e2.
8. Bujold E, Roberge S, Lacasse Y, et al.
Prevention of preeclampsia and intrauterine growth restriction with aspirin
started in early pregnancy: a meta-analysis. Obstet Gynecol 2010;116:402-14.
9. Roberge S, Nicolaides KH, Demers S,
Villa P, Bujold E. Prevention of perinatal
death and adverse perinatal outcome using
low-dose aspirin: a meta-analysis. Ultrasound Obstet Gynecol 2013;41:491-9.
10. Roberge S, Nicolaides K, Demers S,
Hyett J, Chaillet N, Bujold E. The role of
aspirin dose on the prevention of preeclampsia and fetal growth restriction:
systematic review and meta-analysis. Am
J Obstet Gynecol 2017;216(2):110-120.e6.
11. National Collaborating Centre for
Women’s and Children’s Health (UK). Hypertension in pregnancy: the management
of hypertensive disorders during pregnancy. London: RCOG Press, 2010.
12. Wright D, Syngelaki A, Akolekar R,
Poon LC, Nicolaides KH. Competing risks
model in screening for preeclampsia by
maternal characteristics and medical history. Am J Obstet Gynecol 2015;213(1):
62.e1-62.e10.
13. Hypertension in pregnancy: report of
the American College of Obstetricians
and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013;
122:1122-31.
14. O’Gorman N, Wright D, Poon LC, et al.
Multicenter screening for preeclampsia by
maternal factors and biomarkers at 11-13
weeks’ gestation: comparison to NICE
guidelines and ACOG recommendations.
Ultrasound Obstet Gynecol 2017;49:756-
60.
15. Akolekar R, Syngelaki A, Poon L,
Wright D, Nicolaides KH. Competing
risks model in early screening for preeclampsia by biophysical and biochemical
markers. Fetal Diagn Ther 2013;33:8-15.
16. Robinson HP, Fleming JE. A critical
evaluation of sonar “crown-rump length”
measurements. Br J Obstet Gynaecol 1975;
82:702-10.
17. Poon LC, Zymeri NA, Zamprakou A,
Syngelaki A, Nicolaides KH. Protocol for
measurement of mean arterial pressure at
11-13 weeks’ gestation. Fetal Diagn Ther
2012;31:42-8.
18. Plasencia W, Maiz N, Bonino S, Kaihura C, Nicolaides KH. Uterine artery
Doppler at 11 + 0 to 13 + 6 weeks in the
prediction of pre-eclampsia. Ultrasound
Obstet Gynecol 2007;30:742-9.
19. Brown MA, Lindheimer MD, de Swiet
M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for
the Study of Hypertension in Pregnancy
(ISSHP). Hypertens Pregnancy 2001;20(1):
IX-XIV.
20. Poon LC, Tan MY, Yerlikaya G, Syngelaki A, Nicolaides KH. Birth weight in
live births and stillbirths. Ultrasound Obstet Gynecol 2016;48:602-6.
21. R Development Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing, 2011 (http://www.R-project
.org/).
22. Van Buuren S, Groothuis-Oudshoorn
K. Multivariate imputation by chained
equations in R. J Stat Softw 2011;45:1-67.
23. O’Gorman N, Wright D, Syngelaki A,
et al. Competing risks model in screening
for preeclampsia by maternal factors and
biomarkers at 11-13 weeks gestation.
Am J Obstet Gynecol 2016;214(1):103.e1-
103.e12.
24. Roberge S, Villa P, Nicolaides K, et al.
Early administration of low-dose aspirin
for the prevention of preterm and term
preeclampsia: a systematic review and
meta-analysis. Fetal Diagn Ther 2012;31:
141-6.
25. Caron N, Rivard GE, Michon N, et al.
Low-dose ASA response using the PFA100 in women with high-risk pregnancy.
J Obstet Gynaecol Can 2009;31:1022-7.
26. Ayala DE, Ucieda R, Hermida RC.
Chronotherapy with low-dose aspirin for
prevention of complications in pregnancy.
Chronobiol Int 2013;30:260-79.

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